U.S. patent application number 17/287498 was filed with the patent office on 2021-12-23 for neurostimulation artefact minimisation.
This patent application is currently assigned to Saluda Medical Pty Ltd. The applicant listed for this patent is Saluda Medical Pty Ltd. Invention is credited to Dean Michael Karantonis, Jonathan Brereton Scott, Peter Scott Vallack Single.
Application Number | 20210393964 17/287498 |
Document ID | / |
Family ID | 1000005855371 |
Filed Date | 2021-12-23 |
United States Patent
Application |
20210393964 |
Kind Code |
A1 |
Single; Peter Scott Vallack ;
et al. |
December 23, 2021 |
Neurostimulation Artefact Minimisation
Abstract
A neurostimulation device has a stimulus, and a position of a
measurement electrode relative to the stimulus, configured such
that in artefact as arising relative to distance from the stimulus
electrode a minima region of the artefact is substantially
co-located with the measurement electrode. Or, a ratio of the
inter-electrode spacing to the electrode length is between 2 and
3.66. Or, an impedance is connected to a passive electrode and is
configured to reduce artefact arising on the measurement
electrode.
Inventors: |
Single; Peter Scott Vallack;
(Artarmon, AU) ; Karantonis; Dean Michael;
(Artarmon, AU) ; Scott; Jonathan Brereton;
(Artarmon, AU) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Saluda Medical Pty Ltd |
Artarmon |
|
AU |
|
|
Assignee: |
Saluda Medical Pty Ltd
Artarmon
AU
|
Family ID: |
1000005855371 |
Appl. No.: |
17/287498 |
Filed: |
October 23, 2019 |
PCT Filed: |
October 23, 2019 |
PCT NO: |
PCT/AU2019/051160 |
371 Date: |
April 21, 2021 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 1/0551 20130101;
A61N 1/36071 20130101; A61N 1/36139 20130101 |
International
Class: |
A61N 1/36 20060101
A61N001/36; A61N 1/05 20060101 A61N001/05 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 23, 2018 |
AU |
2018904012 |
Claims
1. A neurostimulation device comprising: at least one stimulation
electrode configured to deliver an electrical stimulus to neural
tissue; and at least one measurement electrode configured to record
a response of the neural tissue to the stimulus, wherein the
stimulus and a position of the measurement electrode relative to
the stimulus electrode are configured such that, in artefact as
arising relative to distance from the stimulus electrode, a minima
region of the artefact is substantially co-located with the
measurement electrode.
2. The neurostimulation device of claim 1 wherein artefact arising
upon the measurement electrode is less than 75% of a peak artefact
arising in spatial regions more distal from the stimulation
electrode.
3. The neurostimulation device of claim 2 wherein artefact arising
upon the measurement electrode is less than 50% of a peak artefact
arising in spatial regions more distal from the stimulation
electrode.
4. The neurostimulation device of claim 3 wherein artefact arising
upon the measurement electrode is less than 25% of a peak artefact
arising in spatial regions more distal from the stimulation
electrode.
5. The neurostimulation device of claim 1 wherein the minima region
of artefact comprises a zero crossing region of artefact.
6. The neurostimulation device of claim 1 configured to deliver the
stimulus in a multipolar fashion utilising more than two stimulus
electrodes, and to impose a mismatch on the respective pairs of
stimulation electrodes, in order to thereby co-locate the minima
region of the artefact with the measurement electrode.
7. The neurostimulation device of claim 6, configured to deliver
tripolar stimulus via three stimulus electrodes, comprising a
central electrode which carries an entire stimulus current and two
peripheral electrodes which carry two respective portions of the
stimulus current to maintain charge-balanced stimulation, whereby
the respective portions of the stimulus current carried by the
peripheral stimulus electrodes are mismatched in a manner which
causes the minima region of the artefact to be substantially
co-located with the measurement electrode.
8. The neurostimulation device of claim 6 configured to adaptively
alter a stimulation ratio, being a ratio between the respective
portions of the stimulus current carried by the stimulus
electrodes, depending on which measurement electrode(s) are in
use.
9. The neurostimulation device of claim 8 configured to carry out
artefact minimisation by delivering a range of stimuli of varying
stimulus ratio, at a sub-threshold level which does not recruit a
neural response, observing the artefact caused by each such
stimulus at the measurement electrodes, and seeking a stimulus
ratio which minimises artefact observed upon the measurement
electrodes in use.
10. The neurostimulation device of claim 6, configured to deliver a
quadrupolar stimulation employing four stimulus electrodes.
11. A method of neurostimulation, the method comprising: delivering
an electrical stimulus to neural tissue using at least one
stimulation electrode; and recording a response of the neural
tissue to the stimulus using at least one measurement electrode,
wherein the stimulus and a position of the measurement electrode
relative to the stimulus electrode are configured such that, in
artefact as arising relative to distance from the stimulus
electrode, a minima region of the artefact is substantially
co-located with the measurement electrode.
12. An implantable lead for neurostimulation, the lead comprising a
plurality of electrodes, each electrode having an electrode length
and an electrode width, and the electrodes being longitudinally
spaced apart by an inter-electrode spacing, wherein the electrode
width is greater than the electrode length; wherein the electrode
length is less than 3 mm, and wherein a ratio of the
inter-electrode spacing to the electrode length is between 2 and
3.66.
13. The implantable lead of claim 12 wherein the electrode length
is greater than 1.5 mm.
14. The implantable lead of claim 13 wherein the electrode length
is greater than 1.8 mm.
15. The implantable lead of claim 12 wherein the electrode length
is less than 2.9 mm.
16. The implantable lead of claim 12 wherein the electrode length
is less than 2.2 mm.
17. The implantable lead of claim 12 wherein a ratio of the
inter-electrode spacing to the electrode length is greater than
2.1.
18. The implantable lead of claim 17 wherein the ratio of the
inter-electrode spacing to the electrode length is greater than
2.4.
19. The implantable lead of claim 12 wherein a ratio of the
inter-electrode spacing to the electrode length is less than
3.5.
20. The implantable lead of claim 19 wherein a ratio of the
inter-electrode spacing to the electrode length is less than
2.7.
21. A neurostimulation device comprising: at least one stimulation
electrode configured to deliver an electrical stimulus to neural
tissue; at least one measurement electrode configured to record a
response of the neural tissue to the stimulus; at least one passive
electrode proximal to the measurement electrode; and an impedance
connected to the passive electrode, the impedance being configured
to reduce artefact arising on the measurement electrode.
22. The neurostimulation device of claim 21 wherein the impedance
is a variable impedance, and wherein the device is configured to
adaptively control the variable impedance in order to reduce
artefact observed on the at least one measurement electrode.
23. The neurostimulation device of claim 22 configured to control
the variable impedance by delivering a range of stimuli while
adjusting the variable impedance to take a range of distinct
values, and observing the artefact caused by each such stimulus at
the measurement electrode(s), in order to seek an impedance value
which minimises artefact observed upon the measurement electrode(s)
in use at the time.
24. The neurostimulation device of claim 23 further comprising a
second feedback loop configured to seek a stimulus ratio which
minimises artefact in accordance with claim 9.
25. The neurostimulation device of claim 21, wherein the impedance
is connected between a pair of passive electrodes positioned either
side of the measurement electrode.
26. A method for neurostimulation, the method comprising:
delivering an electrical stimulus to neural tissue using at least
one stimulation electrode; recording a response of the neural
tissue to the stimulus using a measurement electrode; configuring
an impedance connected to a passive electrode proximal to the
measurement electrode, to reduce artefact arising on the
measurement electrode.
27. A neurostimulation device comprising: at least one stimulation
electrode configured to deliver an electrical stimulus to neural
tissue; and at least one measurement electrode configured to record
a response of the neural tissue to the stimulus; wherein the
electrodes are arranged in a longitudinal array and at least one of
the electrodes is configured to exhibit a greater resistance in a
longitudinal direction as compared to a resistance of that
electrode in a transverse direction.
28. A neurostimulation device comprising: at least one stimulation
electrode configured to deliver an electrical stimulus to neural
tissue; a current source configured to produce the electrical
stimulus; and at least one measurement electrode configured to
record a response of the neural tissue to the stimulus; wherein the
stimulation electrode is split into at least two electrode portions
configured to create a discontinuity in a tissue-electrode
interface, and wherein the current source is connected to the
electrode portions by respective resistors.
29. The neurostimulation device of claim 9 wherein a first
resistance connecting the current source to a first portion of the
split electrode is different from a second resistance connecting
the current source to a second portion of the split electrode, in a
manner to counteract asymmetric voltages upon an electrode-tissue
interface.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of Australian
Provisional Patent Application No. 2018904012 filed 23 Oct. 2018,
which is incorporated herein by reference.
TECHNICAL FIELD
[0002] The present invention relates to measurement of compound
action potentials evoked by a neurostimulator, and in particular to
the minimisation of artefact caused by application of an electrical
stimulus.
BACKGROUND OF THE INVENTION
[0003] There are a range of situations in which it is desirable to
apply neural stimuli in order to give rise to a compound action
potential (CAP). For example, neuromodulation is used to treat a
variety of disorders including chronic pain, Parkinson's disease,
and migraine. A neuromodulation system applies an electrical pulse
to tissue in order to generate a therapeutic effect. When used to
relieve chronic pain, the electrical pulse is applied to the dorsal
column (DC) of the spinal cord, referred to as spinal cord
stimulation (SCS). Neuromodulation systems typically comprise an
implanted electrical pulse generator, and a power source such as a
battery that may be rechargeable by transcutaneous inductive
transfer. An electrode array is connected to the pulse generator,
and is positioned in the dorsal epidural space above the dorsal
column. An electrical pulse applied to the dorsal column by an
electrode causes the depolarisation of neurons, and generation of
propagating action potentials. The fibres being stimulated in this
way inhibit the transmission of pain from that segment in the
spinal cord to the brain. To sustain the pain relief effects,
stimuli are applied substantially continuously, for example at a
frequency in the range of 50-100 Hz.
[0004] Neuromodulation may also be used to stimulate efferent
fibres, for example to induce motor functions. In general, the
electrical stimulus generated in a neuromodulation system triggers
a neural action potential which then has either an inhibitory or
excitatory effect. Inhibitory effects can be used to modulate an
undesired process such as the transmission of pain, or to cause a
desired effect such as the contraction of a muscle.
[0005] There are a range of circumstances in which it is desirable
to obtain an electrical measurement of a compound action potential
(CAP) evoked on a neural pathway by an electrical stimulus applied
to the neural pathway. However, this can be a difficult task as an
observed CAP signal will typically have a maximum amplitude of a
few tens of microvolts or less, whereas a stimulus applied to evoke
the CAP is typically several volts. Electrode artefact usually
results from the stimulus, and manifests as a decaying output of
several millivolts or hundreds of microvolts throughout the time
that the CAP occurs, presenting a significant obstacle to isolating
the much smaller CAP of interest. As the neural response can be
contemporaneous with the stimulus and/or the stimulus artefact, CAP
measurements present a difficult challenge of implant design. In
practice, many non-ideal aspects of a circuit lead to artefact, and
as these mostly have a decaying exponential characteristic which
can be of either positive or negative polarity, identification and
elimination of sources of artefact can be laborious. A number of
approaches have been proposed for recording a CAP, including those
of King (U.S. Pat. No. 5,913,882), Nygard (U.S. Pat. No.
5,785,651), Daly (US Patent Application No. 2007/0225767) and the
present Applicant (U.S. Pat. No. 9,386,934).
[0006] Evoked responses are less difficult to detect when they
appear later in time than the artefact, or when the signal-to-noise
ratio is sufficiently high. The artefact is often restricted to a
time of 1-2 ms after the stimulus and so, provided the neural
response is detected after this time window, data can be obtained.
This is the case in surgical monitoring where there are large
distances between the stimulating and recording electrodes so that
the neural response propagation time from the stimulus site to the
recording electrodes exceeds 2 ms. However, to characterize
responses evoked by a single implant such as responses from the
dorsal columns to SCS, for example, high stimulation currents and
close proximity between electrodes are required, and therefore the
measurement process must overcome contemporaneous artefact
directly, greatly exacerbating the difficulty of neural
measurement.
[0007] Similar considerations can arise in deep brain stimulation
where it can be desirable to stimulate a neural structure and
immediately measure the evoked compound action potential produced
in that structure before the neural response propagates elsewhere
in the brain. Artefact remains a significant obstacle to
measurement of neural responses proximal to the stimulus location,
with the consequence that most if not all conventional
neurostimulation implants, which are necessarily compact devices,
do not take any measurements whatsoever of neural responses evoked
by the implant's stimuli.
[0008] Any discussion of documents, acts, materials, devices,
articles or the like which has been included in the present
specification is solely for the purpose of providing a context for
the present invention. It is not to be taken as an admission that
any or all of these matters form part of the prior art base or were
common general knowledge in the field relevant to the present
invention as it existed before the priority date of each claim of
this application.
[0009] Throughout this specification the word "comprise", or
variations such as "comprises" or "comprising", will be understood
to imply the inclusion of a stated element, integer or step, or
group of elements, integers or steps, but not the exclusion of any
other element, integer or step, or group of elements, integers or
steps.
[0010] In this specification, a statement that an element may be
"at least one of" a list of options is to be understood that the
element may be any one of the listed options, or may be any
combination of two or more of the listed options.
SUMMARY OF THE INVENTION
[0011] According to a first aspect the present invention provides a
neurostimulation device comprising:
[0012] at least one stimulation electrode configured to deliver an
electrical stimulus to neural tissue; and
[0013] at least one measurement electrode configured to record a
response of the neural tissue to the stimulus,
[0014] wherein the stimulus and a position of the measurement
electrode relative to the stimulus electrode are configured such
that, in artefact as arising relative to distance from the stimulus
electrode, a minima region of the artefact is substantially
co-located with the measurement electrode.
[0015] According to a second aspect the present invention provides
a method of neurostimulation, the method comprising:
[0016] delivering an electrical stimulus to neural tissue using at
least one stimulation electrode; and
[0017] recording a response of the neural tissue to the stimulus
using at least one measurement electrode,
[0018] wherein the stimulus and a position of the measurement
electrode relative to the stimulus electrode are configured such
that, in artefact as arising relative to distance from the stimulus
electrode, a minima region of the artefact is substantially
co-located with the measurement electrode.
[0019] The minima region of artefact is defined as a spatial region
in which a magnitude of artefact is reduced relative to peak
artefact in spatial regions more distal from the stimulation
electrode. In some embodiments, the minima region of artefact may
comprise a zero crossing region of artefact, being a spatial region
in which a magnitude of artefact is reduced relative to peak
artefact in spatial regions more distal from the stimulation
electrode, and wherein the zero crossing region of artefact
contains a zero crossing of artefact. For example, in some
embodiments the minima region of artefact may comprise a spatial
region in which a magnitude of artefact is less than 75%, more
preferably less than 50%, more preferably less than 25%, of a peak
artefact arising in spatial regions more distal from the
stimulation electrode. Notably, by co-locating the minima region of
artefact with the measurement electrode, allows the measurement
electrode to be positioned closer to the stimulation site and to
thus capture a stronger and less dispersed evoked compound action
potential (ECAP), while suffering from less artefact than would
occur at even some locations which are further from the stimulation
site. In preferred embodiments the stimulus, and a position of the
measurement electrode relative to the stimulus electrode, are
configured such that a minima of artefact such as the zero crossing
of artefact is substantially, or preferably is precisely,
co-located with the measurement electrode, so that the measurement
electrode experiences negligible artefact relative to peak artefact
arising at other distances from the stimulus electrode.
[0020] To this end, in at least some embodiments the present
invention provides techniques relating to the design of stimulation
patterns for spinal cord stimulation and other neuromodulation
methods, and provides a set of methods that may be used to reduce
or null artefact, thus improving measurement of tissue responses to
stimulation such as a neural compound action potential evoked by
the applied stimulus.
[0021] In some embodiments of the first aspect of the invention,
the stimulus is configured so that the minima region of the
artefact is substantially co-located with the measurement
electrode, by delivering the stimulus in a multipolar fashion
utilising more than two stimulus electrodes, and imposing a
mismatch on the respective pairs of stimulation electrodes in order
to co-locate the minima region of the artefact with the measurement
electrode. For example the stimulus may be delivered in a tripolar
fashion by three stimulus electrodes, comprising a central
electrode which carries an entire stimulus current and two
peripheral electrodes which carry two respective portions of the
stimulus current to maintain charge-balanced stimulation, whereby
the respective portions of the stimulus current carried by the
peripheral stimulus electrodes are mismatched in a manner which
causes the minima region of the artefact to be substantially
co-located with the measurement electrode.
[0022] The desired ratio between the respective portions of the
stimulus current carried by the peripheral electrodes, referred to
herein as the stimulation ratio, differs depending on which
measurement electrode(s) are in use. Accordingly, preferred
embodiments provide an artefact minimisation algorithm which
delivers a range of stimuli of varying stimulus ratio, at a
sub-threshold level which does not recruit a neural response, and
observes the artefact caused by each such stimulus at the
measurement electrodes, in order to seek a stimulus ratio which
minimises artefact observed upon the measurement electrodes in
use.
[0023] Other embodiments of the first aspect of the invention may
employ other stimulus configurations in order to cause the minima
region of the artefact to be substantially co-located with the
measurement electrode. For example, a quadrupolar stimulation
configuration employing four stimulus electrodes, or a multipolar
stimulation configuration employing more than four electrodes, may
be employed, and may be preconfigured or adaptively configured to
deliver stimulus ratio(s) which are mismatched in order to
manipulate the location of the minima region of the artefact so
that it is substantially co-located with the measurement
electrode.
[0024] According to a third aspect the present invention provides
an implantable lead for neurostimulation, the lead comprising a
plurality of electrodes, each electrode having an electrode length
and an electrode width, and the electrodes being longitudinally
spaced apart by an inter-electrode spacing,
[0025] wherein the electrode width is greater than the electrode
length;
[0026] wherein the electrode length is less than 3 mm, and
[0027] wherein a ratio of the inter-electrode spacing to the
electrode length is between 2 and 3.66.
[0028] In embodiments of the third aspect, where the lead is a
percutaneous lead comprising cuff electrodes passing substantially
or wholly around a circumference of the lead, or in the case of
non-cylindrical leads around a cross-sectional perimeter of the
lead, the electrode width is defined herein as being equal to a
width or diameter or largest cross-sectional dimension of the
lead.
[0029] In embodiments of the third aspect, the electrode length is
preferably greater than 1.5 mm, for example greater than 1.6 mm,
more preferably greater than 1.8 mm. The electrode length is
preferably less than 2.9 mm, more preferably less than 2.55 mm,
more preferably less than 2.2 mm. The electrode length is
preferably 2.0 mm.
[0030] In embodiments of the third aspect, the ratio of the
inter-electrode spacing to the electrode length is preferably
greater than 2.1, for example being greater than 2.25, more
preferably greater than 2.4. The ratio of the inter-electrode
spacing to the electrode length is preferably less than 3.5, for
example being less than 3.1, more preferably being less than
2.7.
[0031] The ratio of the inter-electrode spacing to the electrode
length is preferably 2.5.
[0032] According to a fourth aspect, the present invention provides
a neurostimulation device comprising:
[0033] at least one stimulation electrode configured to deliver an
electrical stimulus to neural tissue;
[0034] at least one measurement electrode configured to record a
response of the neural tissue to the stimulus;
[0035] at least one passive electrode proximal to the measurement
electrode; and
[0036] an impedance connected to the passive electrode, the
impedance being configured to reduce artefact arising on the
measurement electrode.
[0037] According to a fifth aspect, the present invention provides
a method for neurostimulation, the method comprising:
[0038] delivering an electrical stimulus to neural tissue using at
least one stimulation electrode; recording a response of the neural
tissue to the stimulus using a measurement electrode; configuring
an impedance connected to a passive electrode proximal to the
measurement electrode, to reduce artefact arising on the
measurement electrode.
[0039] In embodiments of the fourth and fifth aspects of the
invention, the impedance may be preconfigured, and fixed. In
alternative embodiments, the impedance may be a variable impedance,
and may be adaptively configured by any suitable means in order to
reduce, or preferably seek a minima in, artefact observed on the
measurement electrode(s). For example the variable impedance may be
adaptively configured by use of an artefact minimisation algorithm
which delivers a range of stimuli while adjusting the variable
impedance to take a range of distinct values, the stimuli being at
a sub-threshold level which does not recruit a neural response, and
observes the artefact caused by each such stimulus at the
measurement electrode(s), in order to seek an impedance value which
minimises artefact observed upon the measurement electrode(s) in
use at the time. Alternatively, this technique may adopt the use of
supra-threshold stimuli which do recruit neural responses, and may
measure the total energy of the neural response+artefact, and may
adjust the variable impedance in such a way as to seek a reduction
or minima of such energy. The artefact minimisation algorithm of
such embodiments may operate simultaneously with the
above-described artefact minimisation algorithm of some embodiments
of the first and second aspects of the invention, for example by
use of two simultaneously or contemporaneously running feedback
loops.
[0040] The impedance may comprise a resistance, or a reactance. The
impedance may be variable by being implemented in the form of a
switched capacitor resistance, configured to present a controllable
resistance as defined electronically by a switching rate or pulse
width modulation of the switched capacitor.
[0041] In some embodiments, the impedance is connected between a
pair of passive electrodes positioned either side of the
measurement electrode. In such embodiments, where more than one
measurement electrode is used, one of the passive electrodes is
preferably positioned between the measurement electrodes, and the
other of the passive electrodes is preferably positioned between
the stimulus electrode(s) and the measurement electrodes. Thereby,
a pair of electrodes not involved in the stimulation or measurement
can be used to steer a minima or zero of artefact onto a
measurement electrode.
[0042] According to a sixth aspect, the present invention provides
a neurostimulation device comprising:
[0043] at least one stimulation electrode configured to deliver an
electrical stimulus to neural tissue; and
[0044] at least one measurement electrode configured to record a
response of the neural tissue to the stimulus;
[0045] wherein the electrodes are arranged in a longitudinal array
and at least one of the electrodes is configured to exhibit a
greater resistance in a longitudinal direction as compared to a
resistance of that electrode in a transverse direction.
[0046] In some embodiments of the sixth aspect, an electrode may be
configured to exhibit a greater resistance in a longitudinal
direction by providing the electrode with transverse slots or ribs,
configured to increase a longitudinal current path length.
[0047] According to a seventh aspect, the present invention
provides a neurostimulation device comprising:
[0048] at least one stimulation electrode configured to deliver an
electrical stimulus to neural tissue;
[0049] a current source configured to produce the electrical
stimulus; and
[0050] at least one measurement electrode configured to record a
response of the neural tissue to the stimulus;
[0051] wherein the stimulation electrode is split into at least two
electrode portions configured to create a discontinuity in a
tissue-electrode interface, and wherein the current source is
connected to the electrode portions by respective resistors.
[0052] In some embodiments of the seventh aspect, a first
resistance connecting the current source to a first portion of the
split electrode is different from a second resistance connecting
the current source to a second portion of the split electrode. The
first and second resistances are preferably selected, or are
adaptively controlled, in a manner to counteract asymmetric
voltages upon an electrode-tissue interface.
BRIEF DESCRIPTION OF THE DRAWINGS
[0053] An example of the invention will now be described with
reference to the accompanying drawings, in which:
[0054] FIG. 1 schematically illustrates an implanted spinal cord
stimulator;
[0055] FIG. 2 is a block diagram of the implanted
neurostimulator;
[0056] FIG. 3 is a schematic illustrating interaction of the
implanted stimulator with a nerve;
[0057] FIG. 4 illustrates an implantable lead electrode array;
[0058] FIG. 5 is an equivalent circuit of a single cuff
electrode;
[0059] FIG. 6 is a plot of predicted artefact amplitude as a
function of the number of sections into which an electrode cuff is
nominally split in a simulation;
[0060] FIG. 7 pictorially depicts a stimulation and measurement
configuration of an electrode lead;
[0061] FIG. 8 is a plot of the stimulus voltage and resultant
saline artefact;
[0062] FIG. 9 is a simplified circuit diagram showing simulated
slicing of four electrodes into two slices each, and interaction
thereof with a mesh resistance representation of saline;
[0063] FIG. 10 is a plot of the simulated potential arising on
interface layers of electrode four as a function of nominal slice
position, in response to a stimulus applied between electrodes two
and one, in a 21 slice simulation, both at the end of the stimulus
and after lms relaxation;
[0064] FIG. 11 is a plot of the simulated potential arising on the
stimulus electrode at the end of the biphasic stimulus, in a 21
slice simulation,
[0065] FIG. 12 is a plot of artefact, both measured and simulated,
as a function of stimulus current;
[0066] FIG. 13 is a plot of artefact, both measured and predicted,
measured between adjacent electrode pairs, as a function of
displacement from the stimulus electrodes;
[0067] FIGS. 14a and 14b are diagrams of current flow paths in two
stimulating electrodes and one passive electrode, during and after
a stimulation pulse respectively;
[0068] FIG. 15 is a simulated plot of electric field in saline
surrounding two stimulating and two passive electrodes shortly
after completion of a stimulus;
[0069] FIG. 16 is a simulated plot of electric field in saline
surrounding two stimulating and one passive electrode shortly after
completion of a stimulus;
[0070] FIG. 17 shows a method of tripolar stimulation for artefact
minimisation;
[0071] FIG. 18 illustrates decomposition of tripolar stimulation
into bipolar stimuli;
[0072] FIG. 19 illustrates artefact summation from the components
of FIG. 18;
[0073] FIG. 20 shows simulated artefact for tripolar stimulation as
the term A is varied;
[0074] FIG. 21 shows a variable tripolar stimulation waveform in
accordance with one embodiment of the invention;
[0075] FIG. 22 shows artefact amplitude on electrodes E4-E8 as the
tripolar stimulus ratio is varied;
[0076] FIGS. 23a-23d illustrate a feedback control loop for
automatically adjusting multipolar stimulation ratios to seek a
minima of artefact, in accordance with an embodiment of the
invention;
[0077] FIG. 24 illustrates another embodiment, in which a birding
resistor minimises artefact;
[0078] FIG. 25 illustrates a 4-contact epidural electrode array
having conventionally sized electrodes, and an epidural electrode
array in accordance with an embodiment of the present invention,
comprising shortened electrodes;
[0079] FIG. 26 shows a circuit model of a single electrode in a
saline bath;
[0080] FIG. 27 shows the voltage along the surface of the electrode
of FIG. 26;
[0081] FIG. 28 shows a circuit model of a pair of stimulating
electrodes in a saline bath;
[0082] FIG. 29 shows the voltage along the surface of the
electrodes of FIG. 28;
[0083] FIG. 30 shows a circuit model of a pair of recording
electrodes in a saline bath;
[0084] FIG. 31 shows the voltage along the surface of the
electrodes of FIG. 30;
[0085] FIG. 32 shows a compression algorithm used to highlight
artefact in FIG. 34;
[0086] FIG. 33 shows a stimulation waveform;
[0087] FIG. 34 shows the compressed field in a saline bath in
response to a biphasic stimulation;
[0088] FIG. 35 shows the uncompressed voltages along the electrode
surface;
[0089] FIG. 36 illustrates a paddle electrode array having
shortened electrodes in accordance with another embodiment of the
invention;
[0090] FIG. 37 illustrates a neurostimulation lead having split
electrodes in accordance with an embodiment of the invention;
[0091] FIG. 38 illustrates another neurostimulation lead having
split electrodes in accordance with another embodiment of the
invention; and
[0092] FIG. 39 illustrates a neurostimulation electrode having
increased longitudinal resistance in accordance with a further
embodiment of the invention.
Description of the Preferred Embodiments
[0093] FIG. 1 schematically illustrates an implanted spinal cord
stimulator 100. Stimulator 100 comprises an electronics module 110
implanted at a suitable location in the patient's lower abdominal
area or posterior superior gluteal region, and an electrode
assembly 150 implanted within the epidural space and connected to
the module 110 by a suitable lead. Numerous aspects of operation of
implanted neural device 100 are reconfigurable by an external
control device 192. Moreover, implanted neural device 100 serves a
data gathering role, with gathered data being communicated to
external device 192 via any suitable transcutaneous communications
channel 190.
[0094] FIG. 2 is a block diagram of the implanted neurostimulator
100. Module 110 contains a battery 112 and a telemetry module 114.
In embodiments of the present invention, any suitable type of
transcutaneous communication 190, such as infrared (IR),
electromagnetic, capacitive and inductive transfer, may be used by
telemetry module 114 to transfer power and/or data between an
external device 192 and the electronics module 110. Module
controller 116 has an associated memory 118 storing patient
settings 120, control programs 122 and the like. Controller 116
controls a pulse generator 124 to generate stimuli in the form of
current pulses in accordance with the patient settings 120 and
control programs 122. Electrode selection module 126 switches the
generated pulses to the appropriate electrode(s) of electrode array
150, for delivery of the current pulse to the tissue surrounding
the selected electrode(s). Measurement circuitry 128 is configured
to capture measurements of neural responses sensed at sense
electrode(s) of the electrode array as selected by electrode
selection module 126.
[0095] FIG. 3 is a schematic illustrating interaction of the
implanted stimulator 100 with a nerve 180, in this case the spinal
cord however alternative embodiments may be positioned adjacent any
desired neural tissue including a peripheral nerve, visceral nerve,
parasympathetic nerve or a brain structure. Electrode selection
module 126 selects a stimulation electrode 2 of electrode array 150
to deliver an electrical current pulse to surrounding tissue
including nerve 180, and also selects a return electrode 4 of the
array 150 for stimulus current recovery to maintain a zero net
charge transfer.
[0096] Delivery of an appropriate stimulus to the nerve 180 evokes
a neural response comprising a compound action potential which will
propagate along the nerve 180 as illustrated, for therapeutic
purposes which in the case of a spinal cord stimulator for chronic
pain might be to create paraesthesia at a desired location. To this
end the stimulus electrodes are used to deliver stimuli at any
therapeutically suitable frequency, for example 30 Hz, although
other frequencies may be used including as high as the kHz range,
and/or stimuli may be delivered in a non-periodic manner such as in
bursts, or sporadically, as appropriate for the patient. To fit the
device, a clinician applies stimuli of various configurations which
seek to produce a sensation that is experienced by the user as a
paraesthesia. When a stimulus configuration is found which evokes
paraesthesia, which is in a location and of a size which is
congruent with the area of the user's body affected by pain, the
clinician nominates that configuration for ongoing use.
[0097] The device 100 is further configured to sense the existence
and intensity of compound action potentials (CAPs) propagating
along nerve 180, whether such CAPs are evoked by the stimulus from
electrodes 2 and 4, or otherwise evoked. To this end, any
electrodes of the array 150 may be selected by the electrode
selection module 126 to serve as measurement electrode 6 and
measurement reference electrode 8. Signals sensed by the
measurement electrodes 6 and 8 are passed to measurement circuitry
128, which for example may operate in accordance with the teachings
of International Patent Application Publication No. WO2012155183 by
the present applicant, the content of which is incorporated herein
by reference. Nevertheless, artefact remains a significant obstacle
to measurement of neural responses proximal to the stimulus
location. The present disclosure first investigates the artefact
phenomenon in more detail, and then provides a number of novel
solutions based on the findings.
[0098] The current pulses delivered through platinum electrodes by
medical implants to recruit neurones give rise to slowly-decaying
voltage tails, called "artefact". These tails make measurement of
evoked potentials following the pulses very difficult. We present
evidence to show that in a typical clinical scenario these tails
are mostly caused by concentration gradients of species induced in
the electrical double layer adsorbed onto the platinum surface of
both stimulating and passive electrodes. A compact model is
presented that allows simulation of these artefacts. This model can
be expected to prove useful in predicting the effectiveness of
techniques to reduce the artefact amplitude.
[0099] Considerable interest has arisen recently in sensing neural
activity in the presence of, and quickly following, neural stimulus
pulses in order to apply feedback in neuromodulation systems. The
evoked compound action potentials (ECAP) synchronised with the
stimulus and measured near the stimulation site betray the extent
of neural recruitment resulting from the pulse. Measured ECAP thus
can be of great assistance both during the implantation surgery and
for automatic adjustment of the stimulus pulse amplitude and locale
in routine use.
[0100] A typical neuromodulation pulse has an amplitude of several
volts, whereas the amplitude of the signal visible at an electrode
as a result of a nerve firing may be only a few microvolts. To be
useful, the evoked responses must be recorded starting within about
a hundred microseconds of the end of the stimulus pulse. To make
the job of the recording electronics even more difficult, the
artefact tails have amplitudes between millivolts and tens of
microvolts depending upon the spacing between the stimulus and
recording electrodes. Sensor electrodes which are closest to the
stimulation site are best positioned to assess recruitment, but
have greater artefact, as ECAP disperses as it propagates from the
recruitment site. It is demanding to design amplifiers capable of
processing these signals for analog-to-digital conversion,
particularly in CMOS.
[0101] In this light, a compact model of the impedance of the
electrode-electrolyte interface is presented. This model uses
Constant-Phase Elements (CPEs) amongst other more common elements
in an equivalent-circuit representation of the interface between
electrode and electrolyte. The model is able to accurately
represent the impedance of the interface. In a circuit simulator
the model allows prediction of the residual voltage and artefact
tails in some circumstances, but not all. As will be seen below,
the model predicts zero artefact in certain circuit configurations,
whereas measurement reveals that significant artefact actually
arises in such configurations. This makes clear that there is a
mechanism at work that is not captured by the single-CPE compact
model.
[0102] Accordingly, the present inventors introduce a
split-electrode model. It has been hypothesized that artefact can
arise not only through residual charge left in the double layer
surrounding an electrode after it conducts a current, but also by
virtue of an uneven distribution of that charge along the surface
of an electrode. Such an uneven charge distribution can arise even
without any net current flowing through the electrode into the
electronics. One might visualise counter-charges in the diffuse
region of the electrical double layer piling up at one end of an
electrode as a result of surface conduction, resulting from fields
generated by the stimulating electrodes. Although for many purposes
a more elaborate model is necessary, this idea of charges piling up
at one end of an electrode suggests a straightforward way that a
compact model might be constructed to simulate the phenomenon.
[0103] In the proposed split-electrode model, the electrode is
split into multiple sections or "slices" that are modelled
separately. The single-branch model of an electrode is replaced
with one having n branches, each contributing 1/n times the total
admittance (area) presented by the original electrode. The branches
are joined together at a single node at the metal side of the
electrode, but are connected only through the resistor mesh
representing the bulk fluid on the fluid side of the interface (as
shown in FIG. 9, discussed further in the following).
[0104] A rotationally-symmetric situation is considered, so that
simulation is straightforward using a two-dimensional
representation, and comparative measurements can be made with a
cylindrical, implantable, platinum electrode array such as an
octrode (eight electrode array) or dodecatrode (twelve electrode
array). A typical implantable lead electrode array with a set of 8
electrodes (cylindrical platinum cuffs), suitable for use as array
150 in the embodiment of FIGS. 1-3, is pictured in FIG. 4. Each
cuff is about 1.3 mm in diameter and 3 mm long, spaced by 4 mm
insulating sections.
[0105] The equivalent circuit of a single cuff, omitting the diodes
and memristors for clarity, is shown in FIG. 5. As can be seen in
FIG. 5, the equivalent circuit of a single 3 mm cuff of the
electrode array becomes a sequence of n parts each with its own
CPE, and each tapping into different geometrical points in the mesh
of resistors representing the electrolyte. While diodes must be
included in such models except for small-signal simulations, such
diodes are omitted from the present Figures for clarity. For
small-signal simulations of scenarios that are safe for use in
humans, the diode-memristor branch elements can be ignored, however
the diodes at least must be included to detect and model nonlinear
Faradaic effects. Base model parameters for the CPE used in the
circuit were obtained, trimmed to show agreement with the impedance
observed looking into electrodes 1 and 2, and scaled according to
the split factor in use. Our simulations use base values of m=1.5,
|Z|=6500.OMEGA., at 1 Hz, and R.sub.S=12 .OMEGA.. The SPICE
equivalent network was generated using a density of k=1.3 from 10
mHz to 500 kHz.
[0106] Resistor mesh values were calculated using a measured value
of saline conductivity of 6400 mm and on a grid selected to suit
the split factor. In this description we will chiefly consider one
particular circuit arrangement, as depicted pictorially in FIG. 7.
Stimulation current is applied to the second cylindrical cuff of
the lead, marked as electrode 2 in FIGS. 4 and 7. The stimulation
current return will be via the first cuff, electrode 1. The voltage
of interest is that appearing between the fourth and seventh cuffs,
electrodes 4 and 7. This represents a typical, clinically-desirable
arrangement for use in a feedback implant. The stimulus pulse will
be a so-called biphasic pulse consisting of +5 mA delivered for 240
.mu.s, zero current for 200 .mu.s, -5 mA delivered for 240 .mu.s,
and finally disconnection of the drive electronics. The form of the
stimulus pulse is not particularly germane to the issue of how
artefact arises so that the solutions presented in the following
can also be applied to other stimulation regimes.
[0107] This configuration was simulated using a single-CPE model
for the electrodes in 0.1x Phosphate Buffered Saline (PBS). In the
case of a single-branch electrode model, absolutely zero artefact
is predicted to appear between electrodes 4 and 7, assuming there
is no load presented by the electronics. However, when the
electrode model is split into ever-greater numbers of slices, the
prediction changes. FIG. 6 dramatically shows the impact. FIG. 6
shows the predicted artefact amplitude as a function of the number
of sections into which an electrode cuff is split, in the SPICE
simulation. FIG. 6 would suggest that splitting the electrodes into
7 or more slices in the simulation will be required to give
reasonable accuracy of artefact amplitude. Accordingly, a split
factor of 11 will be used in the following, except where noted.
Since the resistor mesh representing the electrolyte (shown in FIG.
9) is also split into slices of the same geometric size, say
3/11ths of a millimetre or finer, the number of mesh nodes involved
to simulate an electrode extending over 60 mm of electrolyte can
get quite large. SPICE takes from a few seconds to a few minutes to
run each such simulation on a typical personal computer.
[0108] Comparison with measurement was performed. A Saluda Medical
Pty Ltd "Evoke" implant was used to generate pulses and amplify the
measured signals. The wiring arrangement is depicted pictorially in
FIG. 7. Stimulus is shown delivered to electrode 2 with ground
return via electrode 1. Response is measured at electrode 4 with
respect to electrode 7. The 0.1x PBS was created using Medicago
09-2051-100 PBS tablets and de-ionised water at the rate of 1
tablet per litre. This is a common phantom for tissue in
cerebrospinal fluid (CSF). The received signal is digitised by the
implant, but was also digitised using a Tektronix TPS2014
isolated-input oscilloscope from a test port provided by the
implant IC. The same data can be obtained from the implant, but
only at a lower sample rate, approximately 16k samples per second.
There is an uncertain additive contribution from common mode
signals owing to the implant amplifier's finite Common-Mode
Rejection Ratio (CMRR), which is no worse than 75 dB.
[0109] FIG. 8 shows the stimulus voltage 810 (left axis) and a
typical measured response signal 820 (right axis) for a 5 mA pulse,
applied from the second to the first electrode, and measuring the
voltage present between the fourth and seventh electrodes, as
depicted in FIG. 7. The response 820 measured (in .mu.V, right
axis) between the fourth and seventh electrodes is blanked until
about 800 .mu.s after the start of the stimulus 810 (depicted in V,
left axis). Response 820 is a manifestation of the artefact which
obscures neural measurements in vivo, and it is to be noted that
the dynamic range of artefact 820 is around 150 .mu.V which is
considerably larger than the voltages observed with evoked neural
responses, illustrating the severity of the problem posed by such
artefact. The series of small impulses on the received pulse tail
820 are caused by the implant ADC operation and are not part of the
signal. As can be observed in FIG. 8, the front-end amplifier (FEA)
used to record signal 820 is blanked during the pulse 810, and the
blanking released about 100 .mu.s after the stimulus current
switches off An arbitrary dc offset has been subtracted from the
test port voltage as the Implant Pulse Generator (IPG) FEA is ac
coupled. The array of small spikes spaced about 31 .mu.s is apart
are clock feedthrough associated with the analog-to-digital
conversion inside the implant chip and should be ignored. Switching
spikes are visible on the stimulus voltage trace 810 in FIG. 8.
These cause a contribution to the artefact that does not vary with
stimulus magnitude. As will be seen below this contributes a
constant offset to the magnitude of the measured artefact.
[0110] It proves difficult to obtain agreement between simulation
and measurement of artefact such as that observed at 820 in FIG. 8.
This difficulty is now attributed by the present inventors to
artefact being the sum of several components that to a large degree
cancel each other out. Thus small deviations in any one component,
associated perhaps with a particular cuff (contact, also referred
to herein as an electrode), can give rise to relatively large
variation in final artefact value. We believe this accounts for the
anecdotal observation that observed artefact can be better or worse
on different contacts, for no obvious reason, even in saline where
the inhomogeneity of tissue is not an issue. Our model allows these
components to be identified separately, as follows.
[0111] A first such artefact component is artefact from passive
electrodes. All the electrodes on a lead are exposed to a voltage
gradient along their length during the pulse. Charge accumulates at
one end of each conductive cuff compared to the other. There is
generated a voltage gradient in the tissue or electrolyte in which
the lead is immersed by the dipole of the stimulating and return
electrodes, being electrodes 2 and 1 in this example. Charge is
more easily displaced along the surface of the cuff than the
surrounding medium. Once the pulse is over, even an electrode that
was not electrically connected, and which conducted zero net
current, acquires a charge imbalance along its surface that
manifests itself as a transient net potential difference between
the metal of the cuff and the bulk medium.
[0112] FIG. 9 shows a simplified circuit with 4 electrodes, each
electrode being split into merely two slices. While the simulations
herein used 11 slices, this two slice simplified circuit is
provided to assist in visualising the generation of artefact in
passive electrodes. Arrows in FIG. 9 show current induced by the
stimulus in one end of a passive electrode and out of the other end
of the passive electrode. The present inventors recognise that the
CPEs of each such single electrode become charged by the
"circulating current".
[0113] FIG. 10 plots the simulated potential resulting from
accumulated charge in the interface layers as a function of
position along electrode 4, purely as a result of the 5 mA stimulus
current flowing between electrodes 2 and 1. The electrode was split
into 21 slices for this simulation. Rectangular symbols 1010
indicate the simulated voltage recorded at the end of the biphasic
stimulus pulse depicted in FIG. 8. The dots 1020 represent the
simulated data at lms elapsed time, showing the relaxation. The
electrode was not connected, so net electrode current remains zero
throughout. It is noted that the distribution is not symmetrical
along the length of the electrode, and for example the slice
potential 1010 at the displacement -1.4 mm is about 2.3 mV whereas
the slice potential 1010 at the displacement +1.4 mm is about -1.9
mV. The simulation suggests that the average or net potential is
around 100 .mu.V across electrode 4 from contact to the bulk
saline. The residual potential is larger on individual electrodes
that are closer to the stimulating pair and smaller on ones further
away. This distribution relaxes at the end of the pulse as the
charge redistributes.
[0114] The same mechanism operates on electrode 7, but less than
2.mu.V results, as compared to the net 100 .mu.V on electrode 4.
Thus, a total of 100 .mu.V contribution is made to V(4,7), being
the sensed voltage, chiefly because of the net voltage between the
tissue side and the metallic side of electrode 4. The first
artefact component, being artefact from passive electrodes, is thus
a considerable contributor to the artefact problem.
[0115] A second artefact component is artefact from Stimulation
Electrodes. The stimulating electrode, number 2 in our example,
develops around 25 times the charge gradient along the length of
its surface compared with electrode 4, since one end of it is much
closer to the ground return path provided by the adjacent electrode
1.
[0116] FIG. 11 shows the simulated potential resulting from
accumulated charge in the interface layers as a function of
position along electrode 2 as a result of the 5 mA stimulus pulses.
The simulation data shown in FIG. 11 is at the end of the biphasic
stimulus pulse 810 depicted in FIG. 8. The y-axis units are chosen
to be the same as those in FIG. 10. At the edge of this electrode,
even a stimulus pulse of 5 mA causes nonlinear effects, although
much less nonlinear action would be expected if the current were to
be delivered evenly across the area of the cuff. This large charge
gradient relaxes at the end of the pulse, inducing potential
differences between all the electrodes along the lead. The
contribution to the measured voltage V(4,7) is 100 .mu.V. It is
further noted that the average offset from zero represents the
charge accumulated after the stimulus. The variation of potential
along the electrode shows the charge is accumulated unevenly. The
charge or species concentration in the double layer is not the same
at each point along the electrode.
[0117] The ground return electrode 1 responds in the same manner as
the stimulating electrode 2, but the polarity of its contribution
is the reverse, and it is a different distance from the receiving
pair 4,7. The ground return electrode 1 thus also produces an
artefact contribution to the measured voltage V(4,7). The
difference between the contributions from the stimulating and
ground electrodes is typically .apprxeq.50 .mu.V, for a 5 mA
stimulus. The second artefact component, being artefact from
stimulation electrodes, is thus also a considerable contributor to
the artefact problem.
[0118] A third artefact component is Common-Mode Artefact. The
total charge accumulated across each of the stimulating and return
electrodes between the metal and the medium (as different from the
difference along the cuff purely on the electrolyte side) is many
hundreds of mV, as seen in FIG. 11. The receiving amplifiers in
state of the art Saluda Medical Evoke implants typically have a
common mode rejection ratio (CMRR) in the range of 80dB. The
circuit ground remains connected to the return current electrode.
The average voltage across the ground electrode appears as a
common-mode signal. This gives rise to .apprxeq.50 .mu.V of
additional artefact. The third artefact component, being common
mode artefact, is thus also a considerable contributor to the
artefact problem.
[0119] Noting these components of artefact, it is possible to
address the question of what total artefact is generated by these
mechanisms when they are operating together. FIG. 12 shows artefact
as a function of the peak stimulus current, both measured and
simulated. The three measured traces 1210, 1212, 1214 represent the
normal variation between supposedly-identical leads. Note the
zero-offset on measured traces resulting from common-mode and
switching signals. The difference in magnitudes between the
simulated trace 1220 and the measured traces is attributed to the
ideal nature of the compact model, within which all electrodes are
identical and common-mode signals have no contribution. In the
circumstances, agreement is considered to be excellent.
[0120] FIG. 13 presents measurement and prediction of the artefact
measured between adjacent electrode pairs v(3,4), v(4,5), v(5,6),
v(6,7), and v(7,8), indicated on the x-axis by their respective
displacement in number of electrodes from the stimulus electrodes.
An offset at zero stimulus current of about 20 .mu.V, as observed
in FIG. 12, has been subtracted from measured data shown in FIG.
13. As described in the preceding, a stimulus of 5 mA is applied at
electrode 2 with ground return through electrode 1. The simulation
predicts the paradoxical change in sign of the artefact between the
first electrode pair (v(3,4), displacement of 1) and second
electrode pair (v(4,5), displacement of 2). This change in sign of
artefact has previously been observed but appeared paradoxical and
added considerable intractability to the problem of solving
artefact. That this change in sign is predicted by the present
model lends considerable confidence to the veracity of the model.
Moreover, this indicates that there exists a zero-crossing of
artefact, or more generally a zero crossing region indicated by
1310, which presents an opportunity for low-artefact neural
measurement, an observation exploited by the presented embodiments
of the present invention.
[0121] A fourth artefact component is the contribution from a
single passive cuff electrode. The impact of charges "passively
displaced" by flowing stimulus currents is key to understanding,
and cannot be underestimated. To emphasise this point and aid
understanding, consider FIG. 14, which is a diagram of current flow
paths in the simplified case of two stimulating and one passive
electrode, during (FIG. 14a) and then after (FIG. 14b) a
stimulation pulse. The current labelled "5" may be 100 times
smaller than currents "1", "2", and "3", but it leaves e3 with
significant displaced charge. This diagram suggests how a
completely passive metal structure becomes "charged", that is how
it comes to host a displaced population of mobile species in the
Gouy-Stern-Chapman layer.
[0122] FIGS. 15 and 16 then show the impact on residual field of
including or omitting a single passive cuff. FIG. 15 is a plot of
electric field in the saline surrounding a set of electrodes
shortly after removal (completion) of a stimulus, for two
stimulating and two passive electrodes. The electrodes are placed
along the y-axis. The electrodes are completely disconnected, so
that no current flows into or out of the electrolyte. FIG. 16 is a
plot of electric field in the saline surrounding a set of
electrodes shortly after removal of stimulus, for two stimulating
and one passive electrodes; in comparison with FIG. 15 the only
change in FIG. 16 is that one of the passive electrodes (e3) has
been removed. Comparison of these two figures quickly reveals that
an added piece of passive disconnected metal (in FIG. 15)
introduces new regions (around slice 100 in the vicinity of
electrode e3) where the field changes polarity, passing through
zero, where there was before (in FIG. 16) no zero at all. Of
course, this phenomenon will occur with any metallic structure in
proximity of the stimulating electrodes, not only components of the
implanted lead itself
[0123] The observation that this electrode model only predicts
artefact at all when the electrode is modelled as a parallel series
of "slices" that are free to accumulate unequal charges confirms
the conjecture that uneven charge distribution on the surface of
individual electrodes contributes to the long pulse tails referred
to as "artefact" observed on implanted measurement electrodes. It
is further noted that the model shows that surface charge imbalance
is the main or possibly sole contributor to artefact, as FIG. 12
demonstrates that the model can account for the magnitude of
artefact observed in a well-designed implant with good common mode
rejection ratio in the front end amplifier used for recording.
[0124] The preceding analysis thus provides confirmation of an
electrode-intrinsic mechanism responsible for electrode artefact.
By "electrode-intrinsic" we mean a phenomenon that is an
inescapable physical consequence of the electrode design, inherent
to the geometry and materials of the electrode, and independent of
electrical action, connection, or loading of associated
electronics. While electrical efforts to minimise artefact tails in
neuromodulation systems arising from electrical action, connection,
or loading of associated electronics are important and ongoing, it
is clear that the artefact measured in the present description
inescapably arises within the electrode-electrolyte system itself.
Thus, even a perfect front end amplifier will encounter this
signal.
[0125] Armed with the new understanding that surface charge
equilibrium will set a lower (best case) limit on the artefact
which will necessarily be added to (i.e. arise contemporaneously
with, and obscure) an evoked compound action potential, it becomes
possible and important to consider how electrodes might be designed
to intrinsically minimise the phenomenon, and also to consider what
electrical steps might be taken to accommodate or even beneficially
exploit this electrode-intrinsic mechanism and the findings of the
preceding analysis. The following solutions are proposed.
[0126] Specifically, we describe several techniques conceived on
the basis of the findings of the preceding analysis. These
techniques include tripolar stimulation, bridged electrodes, and
changes to electrode size and shape, any or all of which may be
implemented in accordance with embodiments of the present
invention.
[0127] Referring again to FIG. 13, it is noted that the sign of the
artefact changes as position changes along the lead with increasing
distance from the stimulation electrode. In particular, when
measuring V(3,4) at a displacement of 1 electrode, the artefact is
negative, but when measuring V(4,5) at a displacement of 2
electrodes from the stimulation electrode, and at greater
displacements, artefact is positive. This is confirmed both by
simulation and by measurement, as indicated in the graph of FIG.
13. While not shown in FIG. 13, other measurement electrode
configurations, such as measuring V(3,5) or V(3,6) can also
experience such a change in sign of artefact with changing
displacement from the stimulation site.
[0128] The first aspect of the present invention recognises that
this change in sign of artefact with increasing displacement from
the stimulation electrode suggests that there exists at least one
location along the lead where the sum of the artefact components is
zero. We therefore turn to consider ways in which the artefact may
be minimized or substantially eliminated at the location of the
measurement electrode, even if artefact is non-zero at locations
away from the measurement electrode, by causing the location of a
zero-crossing of artefact to be substantially co-located with a
measurement electrode. We propose that this may be effected in one
or more of a number of ways, including by means of changing the
layout of electrodes, changing the interconnection of the
electrodes, and/or changing the spatio-temporal distribution of
stimulus current delivered.
[0129] The present embodiments recognise that artefact zero can be
steered with careful tripolar stimulation. In particular, the
present inventors recognise that the artefact zero can be displaced
onto the 4th electrode by adding some contributory current to the
3rd electrode, so that the 2nd and 3rd electrodes combined provide
the stimulus current that is returned via the 1st electrode. In
general, the principle is to stimulate through three or more
electrodes in some fashion, often utilising an asymmetric current
division, in a manner that minimises artefact on another electrode
or electrodes.
[0130] In saline, simulation predicts that there will be a zero of
artefact on electrode 4 when stimulus current X flowing into
electrode 1 is fed by yX out of electrode 2 and (1-y)X is fed out
of electrode 3. Measurement puts these currents close to 0.5.times.
and 0.5.times. respectively, y=0.5.
[0131] FIG. 17 shows a method of tripolar stimulation where the
current to the outer-contacts can be varied using a parameter
alpha. A concise terminology is required to describe general
methods of dividing current between multiple electrodes: the term
[E,e,A] is used to describe injecting a proportion "A" of the total
current C driven between electrode E and electrode e. In this
notation an indifferent electrode, the "earth" point of the system
is defined as electrode 0. This could also be written [1,2,1]. A
list of such definitions describes a complete distribution pattern.
e.g. [1,0,1],[2,0,-1] describes a bipolar stimulation of between
electrodes 1 and 2. Since scaled versions of the same stimulation
pattern is applied to different electrodes, this definition is
independent of the amplitude or waveform which can be biphasic,
triphasic or any other waveshape. For both bipolar, and tripolar,
the convention is that the second phase is cathodic for the
stimulating electrode. This is done to put the nerve activation as
late as possible.
[0132] Tripolar stimulation is described herein by the general
definition [X,x,A],[Y,y,-1],[Z,z,1-A] where X,Y,Z are contact
numbers, x,y,z are the nodes to which each of the other ends of the
current sources are connected. In this document in most cases
x=y=z=0 as it can be simpler to explain the situation of current
sources between electrodes. Usually X <Y <Z indicating that
the electrodes numbers are sequential and A<1. If A=1 or A=0
this becomes bipolar stimulation.
[0133] FIG. 18 shows that tripolar stimulation can be decomposed
into two bipolar stimuli occurring simultaneously. FIG. 19 shows
how the artefact from these two components will appear at the
amplifier output. They will be of opposite phase and the artefact
from the more distant electrode pair will be of lower amplitude.
However, by adjusting the relative amplitude of the two bipolar
stimuli, these components would be expected to cancel. Note in FIG.
18 that the central current source e2 could be omitted and replaced
by a ground connection or by a switched connection to whichever
voltage supply rail is appropriate for cathodic or anodic
operation.
[0134] FIG. 20 shows simulated artefact for tripolar stimulation as
the term A is varied--showing it has a null as expected. The null
occurs for A approximately equal to 0.7. This illustrates that the
method described in FIG. 19 works in principle. FIG. 20 also shows
that the ideal current ratio for creating an artefact null on E4
(being a ratio of about 0.4) is different to that from E5-E8, the
latter all enjoying an artefact null at the same current ratio
(about 0.7). Preferred embodiments would thus utilise differential
neural measurements between two of E5-E8 so as to avoid E4, and
allow artefact to be best minimised on both measurement electrodes
simultaneously. This method of varying the current ratios in
tripolar stimulation to achieve an artefact null represents one
aspect of the invention. Other embodiments of the invention may
employ quadrupolar stimulation in order to steer an artefact minima
to be co-located with a measurement electrode. Other embodiments of
the invention might seek an observed minima in artefact which
occurs when obtaining a differential measurement between two
measurement electrodes, not when artefact on each electrode
measurement electrode is zero or at a minima, but rather when the
magnitude of artefact on each measurement electrode is the same, as
occurs for example at a ratio of 0.2 if using E4 and E6 in FIG.
20.
[0135] Quadrupolar can be described by the notation
[1,0,A,B],[2,0,A.(1-B)],[3,0,-1],[4,0,1-A] where 0<A<1 and
0<B<1. "A" describes the charge division between the
electrodes E1 and E2, and E3, which are proximal and distal to E3,
while B defines the distribution of charge between E1 and E2. FIG.
21 shows a typical stimulation waveform for the case A=0.75, B=0.5.
From this waveform it can be observed that the cathodic stimulation
on E3 is more than twice the amplitude of the cathodic stimuli on
the other electrodes. As a result E3 will be the only electrode
producing an ECAP. It will also be observed that as there are three
electrodes besides E3, and there are different combinations of
charge distribution on the three electrodes where none of them have
a current exceeding 50% of E3, and therefore there is an
opportunity to adjust these ratios to create an artefact null while
only generating a single ECAP. FIG. 22 shows the artefact amplitude
on electrodes E4-E8 as the ratio A is varied. This shows there is
an artefact null at A approximately equal to 0.7.
[0136] When A is equal to 0.7, and assuming the resistances of the
electrodes are similar, the proportion of current in E1, E2 and E4
will be 35%, 35% and 30%. A similar effect would be expected when
electrodes E1 E2 and E4 are simply connected together, which under
the constant impedance approximation will result in division ratios
of 33%, 33% and 33%. This is supported by clinical observations
made by the present Applicant that in general "adding anodes
reduces artefact". As the respective electrode impedances may not
be the same, it may be that using individual current sources on
each electrode provides a more robust result. Simulations indicate
that the artefact reaches a null with a current division set to
37.5%, 37.5%, and 25%, with the null appearing at a similar ratio
on E5 to E6 (E5 is the first available recording electrode in
quadrupolar stimulation; E4 in tripolar stimulation). This
quadrupolar approach thus represents a further aspect of the
invention. It will be appreciated that this multipolar method can
be extended as long as the number of return electrodes is greater
than 2. For example, a stimulation profile of
[1,0,A/2],[2,0,A/2],[3,0,-1],[4,0,(1-A)/2],[4,0,(1-A)/2] would be
expected to produce an artefact null while maintaining conditions
for a single cathode on E3.
[0137] Another embodiment of the present invention is described as
a variant of tripolar stimulation [X,0,A],[Y,0,-1],[Z,0,1-A] where
X,Y and Z are any three electrodes, where Z is used as a recording
electrode, 0<A<1. Thus, in this embodiment artefact is nulled
by injecting a small amount of current into a recording electrode,
whereby artefact can thus be titrated.
[0138] Another variant embodiment of tripolar stimulation may
utilise automatic adjustment. In this embodiment the parameter A is
adjusted automatically to minimize artefact, and it is embedded in
a feedback loop to maintain an evoked response at a preset level.
It is illustrated in FIG. 23. This embodiment has an ECAP feedback
loop consisting of an ECAP detector and the SCS loop controller
which generates a current value I. The present embodiment further
provides for a second feedback loop configured to minimize
artefact, this second loop comprising the ac energy detector, the
artefact loop controller, and the current source controller. This
second loop controls the parameter A that controls the division of
current between electrodes 1 and 3.
[0139] The detector for the artefact loop measures the total energy
on the recording electrodes. This energy will include both ECAP and
artefact. However, the distribution of current between the cathodes
will not affect the ECAP as the current remains constant. However,
this variation in distribution will affect the artefact. At the
point where the artefact is zero, only the ECAP will remain. The
artefact nulling feedback loop operates by first measuring the
total energy of the signal. This is best done by measuring the
standard deviation of the signal samples over the measurement time.
Such a measure is immune to the DC offset in the signal, based on
the definition of standard deviation. The artefact loop controller
then adjusts the control parameter A. Initially, this change can be
in either direction. The artefact loop controller then measures the
total energy a second time, to determine if it has increased or
decreased. The artefact loop controller then changes the value A in
the direction that decreases the detected energy.
[0140] In another embodiment, the architecture of FIG. 23 may be
adapted for sub-threshold determination of a preferred value for
the parameter A. This embodiment provides an artefact minimisation
algorithm which delivers a range of stimuli of varying stimulus
ratio, at a sub-threshold level, being a stimulation level which is
non-zero but which is small enough that it does not recruit any
neural response. The artefact caused by each such sub-threshold
stimulus at the measurement electrodes is then observed, in order
to seek a stimulus ratio A which minimises artefact observed upon
the measurement electrodes. This value of A is then used to
configure a stimulus ratio of supra-threshold stimuli in ongoing
therapeutic stimulation. The present inventors have found that a
value for A which is optimised to minimise artefact at
sub-threshold stimulus levels surprisingly is also well suited to
minimising artefact at supra-threshold stimulation currents.
[0141] Options for current division are shown in FIG. 23c. FIG. 23c
makes use of the symbol key shown in FIG. 23b. The boxes are
symbols for an electrode and its connection. A grey box indicates a
current return (ground) connection for that electrode. A white box
indicates a current source connection for that electrode, with the
percentage of current for that electrode shown. Recording
electrodes on the right are connected to the amplifier inputs.
Recording electrodes are not shown in FIG. 23c for brevity.
[0142] As shown in FIG. 23c, bipolar stimulation uses a single
current source and a ground return. Tripolar stimulation uses two
ground returns, usually on either side of the stimulating
electrode. This is referred to in this document as "passive
tripolar" to avoid ambiguity. In contrast, active tripolar connects
the central contact to ground and connects current sources to the
outer electrodes. 50/50 active tripolar is similar in behaviour to
passive tripolar if the electrode impedances are equal, but the
current division ratio will vary with tissue impedance, and thus
over time as tissue grows around the stimulating electrode. Active
tripolar is thus a preferred method to passive tripolar. Both
passive tripolar and 50/50 active tripolar reduce artefact compared
to bipolar stimulation, particularly for the adjacent electrode (as
has been discussed herein). The present inventors have recognised
that one particularly preferred method is to use active tripolar
with a 75/25 current division ratio as this produces nulls at
several of the recording contacts at the same time. Active tripolar
or multipolar may in some embodiments even provide current sources
for all stimulation electrodes, with no stimulus electrode being
grounded, provided that the net cathodic current in each stimulus
phase is balanced with the net anodic current in that phase. In
such embodiments any mismatch in the current source matching may be
addressed in accordance with the teachings of International Patent
Publication No. WO2014071446, the content of which is incorporated
herein by reference.
[0143] A further method is to use passive quadrupolar. Assuming
equal tissue impedance on all return electrodes, this achieves a
33/33/33 current division ratio, although it is noted that this
simplistic assumption ignores the unequal distance of the
respective grounded return electrodes which will tend to cause
unequal return current division ratio. Nevertheless passive
quadrupolar is preferred compared to passive tripolar as it
produces lower artefact due to this difference in current division.
Passive quadrupolar does however require room on the lead for an
additional stimulating electrode. An active quadrupolar division
ratio of 37.5/37.5/25 has similar artefact characteristics to 75/25
tripolar. There are many variants on these methods depending on the
exact patient circumstances. However, the principles have been
illustrated and so it is to be appreciated that such other variants
are within the scope of the present invention.
[0144] FIG. 23d further illustrates multipolar stimulation
configurations in accordance with some embodiments of the present
invention, alongside some of the measurement electrode
configurations which might be used. FIG. 23c shows stimulation
configurations for use with an implanted lead comprising 12
electrodes. While FIG. 23c shows electrodes 1-3 as being used for
tripolar stimulation, and shows electrodes 1-4 being used for
quadrupolar stimulation, other embodiments may deliver stimuli from
any suitable subset of the 12 electrodes as described above in
relation to FIGS. 1 and 2. In FIG. 23d, each row shows a different
electrode stimulation configuration. Stimulation configuration B,
for example, shows a tripolar stimulation configuration with a
central stimulating electrode (2) and two lateral return electrodes
(1 and 3) connected together. If tissue were homogenous, 50% of the
current would return via each return, but because this varies with
tissue impedance and may also change with posture the respective
return currents cannot be assured. Thus, each return current value
is shown in brackets, and the exact value of the respective return
current through the return electrodes 1 and 3 (or electrodes 1, 2
and 4 in configuration E, for example) will depend on the patient
anatomy. Once again, as shown in Row D, one particularly preferred
method is to use active tripolar with a 75/25 current division
ratio with the larger return current being forced away from the
measurement electrodes. As shown in the stimulation configurations
of FIG. 23d, any other electrodes of the lead may be selected as
the measurement electrodes, and any one of the three or four
electrodes closest to the stimulus may be chosen as the sense
electrode with the farthest electrode (12) being used as the
measurement reference electrode.
[0145] It is to be noted that some of the stimulation
configurations presented in FIG. 23c, or more broadly throughout
the other described embodiments, may not produce a zero-crossing in
artefact. Additionally or alternatively, depending on a type of the
measurement circuitry used, only a power output of the sensed
signal may be retrieved. In such cases, a zero-crossing artefact
may not exist or may not be detected. However, the present
embodiments of the invention nevertheless recognise that a spatial
minima in artefact may be produced and that steps may be taken in
order for the minima to be "steered" or deliberately positioned
upon or proximal to a measurement electrode.
[0146] A further approach to reducing artefact is that a pair of
electrodes not involved in the stimulation or measurement can be
used to steer a zero onto a measurement electrode, as shown in FIG.
24.
[0147] In the example of FIG. 24, simply adding a resistance
between electrodes 3 and 5 will permit artefact to be reduced close
to zero on electrode 4 by adjustment of the joining resistance.
Simulation predicts a value of 400 Ohms for the case above.
Measurement is closer to 200 Ohms, which is quite good agreement.
The resistance can be provided by switching an impedance realized
by pulse-width modulating the connection. There may exist a number
of such "bridge" connections that permit control of the artefact
magnitude, and all such bridging resistor arrangements are within
the scope of the present invention.
[0148] A third approach to artefact minimisation is to change the
number, size and disposition of electrodes in a multi-electrode
lead to minimize artefact on electrodes adjacent to stimulating
electrodes.
[0149] Refer again to FIG. 13. The graph was measured on standard
leads with 3 mm electrodes and 4 mm insulating spaces for a 7 mm
period. Most simply, it is possible that a lead can be constructed
with a small sensing electrode at the zero crossing, where minimum
artefact will be measured. Simulation suggests that the 3rd and 4th
electrodes are instrumental in creating the null, so they are left
as before, and a small electrode is added at the correct position
to sit in the zero between the 3rd and 4th electrodes. There will
exist more than one pattern of electrodes and insulators that
leaves an electrode at an artefact zero, and such variations are
within the scope of the present invention.
[0150] A further solution offered by the present invention involves
a revised electrode design that, in a preferred embodiment, reduces
artefact by 1/3 compared to current state of the art electrode
designs. FIG. 25 in the upper portion shows a 4-contact version of
a current state-of-the-art epidural electrode. Most such electrodes
have 8 contacts, each being 3 mm long and positioned apart on a 7
mm pitch, as shown. In contrast, the preferred embodiment as shown
in the lower portion of FIG. 25 provides for 2 mm long contacts on
a 7 mm pitch.
[0151] In FIG. 25, some electrodes are marked `S` to denote
stimulation electrodes and some are marked `R` denoting recording
electrodes. It will be appreciated that the electrodes are
substantially identical and any electrode can be used for
stimulation and recording. However, this nomenclature is introduced
at this point to support subsequent description. FIG. 25 shows a
situation where a 4-contact lead might be used for stimulation in a
feedback SCS system, with two stimulating and two recording
electrodes. In a system with 8 or 12 electrodes many more
combinations of uses of the electrodes are available, as will be
understood.
[0152] FIG. 26 shows the circuit model of a single electrode in a
saline bath subject to a current that flows along the electrode.
This would be rostro-caudally in a SCS situation. In this Figure
the 3-dimensional structure of the saline bath is modeled as a
2-dimensional array of resistors and the electrode is modeled as a
series of constant phase elements (CPEs), as described in the
preceding. However, in FIG. 26 the resistor mesh and CPE have been
extended to show more resolution, and the electrode becomes a
series of CPEs connected directly on the metallic side but
distributed on the saline side. It has been found experimentally
that 7 slices or more are required to adequately describe a 3 mm
electrode, though 4 are shown in this diagram for clarity, and this
is a discrete model of a continuous situation and thus does not
bear on the outcome. In this diagram the resistors at the perimeter
are not connected. In practice this mesh will end at the limits of
the physical volume it models.
[0153] From this diagram it will be appreciated that if a voltage
is applied between the right and left sides of the mesh, current
will flow, and some will flow into the left-most CPE and then into
the metallic electrode and this will then flow out of the
right-most CPE. Current will also flow symmetrically, but to a
lesser extent, through the centre two CPE elements. Consequently,
at the end of some period, the voltage along the surface of the
array, with respect to the metal, will be as shown in FIG. 27.
[0154] Now consider a pair of adjacent stimulating electrodes shown
in FIG. 28. Current will flow preferentially where the contact
metal is closest. After a period of stimulation, the voltage on the
electrode surface relative to the metal will be as shown in FIG.
29.
[0155] Now consider a pair of adjacent recording electrodes shown
in FIG. 30. The stimulating pair, on the left but not shown, will
create a vertical current gradient in the mesh. This will spread
throughout the resistor mesh, affecting the closer recording
electrode more than the more distant recording electrode. This
current will be a fraction of the total stimulating current so is
denoted with a small letter i. After a period of stimulation, the
voltage on the recording electrodes' surface relative to the metal
will be as in FIG. 31.
[0156] This again illustrates the main mechanisms of artefact
generation: a voltage along a recording electrode which is greater
for electrodes closer to the stimulation source and a gradient on
the stimulating electrode which is largest on the edges where the
stimulating contacts are close to one another. Artefact then occurs
as this charge redistributes during the recording period, creating
a changing differential voltage between the recording electrode
metal contacts. The above-described simulations have shown that
these effects are of comparable magnitude.
[0157] These phenomena are caused by dipoles created on the
stimulating and recording electrodes. A dipole creates an
electrical moment proportional to size and distance between the
opposing charges. Thus reducing the length of the dipole will
reduce the field and thus the artefact. As the dipole is made
unbalanced by the proximity of the stimulating electrodes (as in
FIG. 29), increasing the gap between the electrodes is expected to
lead to more symmetric charge distribution, and thus a smaller
dipole. Simulations have shown that reducing the length of the
electrode from 3 mm to 2 mm reduces the artefact by a factor of 3.
This indicates that both mechanisms are present.
[0158] These phenomena can be seen in simulations of this shortened
electrode configuration. The simulation was performed using the
methods described in the preceding. FIG. 32 shows the compression
algorithm used to highlight the phenomenon in a two-dimensional
field plot. FIG. 33 shows the stimulation waveform, providing a
reference for the subsequent graphs. FIG. 34 shows the compressed
field in a saline bath at various times in response to a biphasic
stimulation. FIG. 35 shows the uncompressed voltages along the
electrode surface.
[0159] The system implications of reducing electrode size include
the following. The impedance of an electrode varies with its area,
and thus its length. Reducing an electrode length from 3 mm to 2 mm
increases its impedance (as simulated in a saline bath with 1/10
saline in tripolar mode) from 750 to 950 ohms. This will increase
the power required to drive the electrode and thus reduce battery
life. However, this trade-off is acceptable and can be recovered by
other system design changes such as improved current delivery
mechanisms as per Australian
[0160] Provisional Patent Application No. 2018900480, the content
of which is incorporated by reference.
[0161] Another system implication pertains to safe charge. The
maximum charge that can be delivered through an electrode before
unsafe radicals (such as Cl and H) are generated depends on the
electrode area. A 3 mm.times.1.3 mm electrode can be used to
deliver 14.5 uC. Since most patients require a charge less than 7
uC to achieve comfort, and an electrode with a 2 mm length can
deliver 9.7 uC before reaching its unsafe limit, an electrode
length of 2 mm is thus more than adequate.
[0162] While FIGS. 25 to 35 are concerned with lead electrodes,
paddle electrode contacts may also be made shorter in the
rostral-caudal dimension in order to improve artefact suffered by
such arrays. FIG. 36 on the right side illustrates the shortening
of contacts for this purpose in accordance with one embodiment of
the invention.
[0163] FIG. 37 illustrates yet another embodiment of the present
invention which exploits the preceding observations. In this
embodiment each stimulating electrode is split into two rings that
are independently driven. Splitting each electrode into two
portions ensures that each portion of the electrode carries the
same current, 1/2. This arrangement will thereby counteract the
asymmetrical voltages arising across a single electrode as shown in
FIG. 35. Similarly splitting the recording electrodes during
stimulation blocks the current through the ring and thus
counteracts the development of voltage asymmetries upon the
recording electrode. The two portions of the recording electrode
can be electrically connected together during the recording phase
by means of the switch 3702 if required. The second recording
electrode (not shown) would have a similar arrangement. While the
embodiment of FIG. 37 utilises two current sources for each
stimulation electrode, with one current source being associated
with each portion of an electrode, in another embodiment current
flowing along the ring of the electrode can instead be attenuated
by using split electrodes and adding resistance to the lead wire as
shown in FIG. 38. This resistance can be added as individual
components or by using connection wire with insulated strands,
where each strand goes to a single ring.
[0164] A further variant is illustrated in FIG. 39. This embodiment
involves adding resistance in a direction specific manner, whereby
resistance is preferentially increased in a direction along the
length of the contact using the contact material itself. This
resistance inhibits the current flow and the development of the
asymmetric voltage distributions associated with artefact as
described in the preceding. In the embodiment of FIG. 39, the
additional longitudinal resistance is added by cutting slots into
the ring. To achieve resistance comparable to the tissue impedance,
the slots increase the current path length and thus the resistance.
The ring is fed from a contact in the middle. To fabricate such
slots might be performed using laser etching.
[0165] Some embodiments of the invention may utilise 3D printing
for construction of the device. Accordingly, in some embodiments
the present invention may reside in a digital blueprint comprising
a digital file in a format configured for use with rapid
prototyping and computer aided design (CAD) and/or manufacturing,
such as being in the STL (stereolithography) file format. Such
digital blueprint files, whether produced by performing a three
dimensional scan of an embodiment of the invention, or produced by
a CAD development software tool, or the like, are within the scope
of the present invention.
[0166] Some embodiments of the present invention may be implemented
in conjunction with other techniques of artefact minimisation or
remediation, including for example the use of a triphasic
stimulation technique in accordance with the teachings of the
present Applicant's International Patent Publication No.
WO2017219096, the content of which is incorporated herein by
reference.
[0167] It will be appreciated by persons skilled in the art that
numerous variations and/or modifications may be made to the
invention as shown in the specific embodiments without departing
from the spirit or scope of the invention as broadly described. The
present embodiments are, therefore, to be considered in all
respects as illustrative and not limiting or restrictive.
* * * * *